Altered default mode network and glymphatic function in insomnia with depression: A multimodal MRI study.

OBJECTIVES

This study aims to evaluate functional changes in the default mode network (DMN) and glymphatic system in individuals of chronic insomnia disorder (CID) with comorbid major depression disorder (MDD).

METHODS

A total of 112 CID patients and 56 healthy controls with good sleep (GS) were enrolled. CID patients were divided into were further divided into a CID-only group and a group with CID and comorbid MDD. Resting-state functional magnetic resonance imaging (rs-fMRI) assessed DMN dysfunction and its connectivity with external networks. To determine whether comorbid MDD exacerbated the decline in glymphatic function in patients with CID, the diffusion tensor imaging along the perivascular space (DTI-ALPS) index was calculated. Binary logistic regression identified key imaging features for diagnostic modeling.

RESULTS

Patients with CID and comorbid MDD exhibited significantly weakened functional connectivity within the DMN. In contrast, the key node posterior cingulate cortex(PCC) of the default mode network showed enhanced functional connectivity with brain regions outside the DMN, including middle cingulate cortex and supplementary motor area. Regarding the glymphatic system, the lower ALPS index in CID patients with comorbid MDD was lower than in CID patients, indicating reduced glymphatic function compared to those without depression. HAMD scores were significantly associated with bilateral Dyproj values (P < 0.001) and the functional connectivity values of PCC_L-SMA_L and TempP_L-PHC_L (P < 0.01). The diagnostic model developed based on these findings demonstrated high diagnostic efficacy for CID with comorbid MDD.

CONCLUSION

The destabilization of subsystems within the DMN may represent the neurological mechanism through which depression contributes to insomnia. Comorbid depressive disorders may exacerbate glymphatic dysfunction in patients with CID, highlighting the importance of early clinical intervention for depressive symptoms in insomnia disorder.